phenylalanine-X-tyrosine-aspartate (FXYD) family; FXYDs are small single-transmembrane proteins that act as novel regulators of Na+/K+-ATPase (NKA). The transmembrane domain and the conserved Phe-X-Tyr-Asp motif of FXYD play a role in the binding of FXYD to the alpha- and beta-subunits of NKA. PFXYD (proline-phenylalanine-X-tyrosine-aspartate) at the beginning of the signature sequence is invariant in all known examples in mammals and identical except for the proline in other vertebrates; X is usually Y (tyrosine), but can also be E, T, or H (glutamate, threonine, or histidine). The FXYD protein family contains at least twelve members that have the extracellular FXYD motif, transmembrane domain, and intracellular domain. Members share a 35-amino acid signature sequence domain, beginning with PFXYD and containing 7 invariant and 6 highly conserved amino acids. In mammals, members of the FXYD family include FXYD1 (phospholemman, PLM), FXYD2 (the gamma-subunit of NKA), FXYD3 (mammary tumor marker Mat-8), FXYD4 (corticosteroid hormone-induced factor, CHIF), FXYD5 (dysadherin), FXYD6 (phosphohippolin), and FXYD7. In elasmobranchs, FXYD10 (phospholemman-like protein from shark, PLMS) was first identified in the rectal glands of Squalus acanthias. In addition, studies on sharks reported that the functions of FXYD10 via its C-terminal cysteine residue interactions were associated with negative regulation of shark NKA activity. Teleostean FXYD proteins (FXYD2, 5-9, 11, and 12) have been reported in certain teleosts such as the Tetraodon nigroviridis, Salmo salar, Danio rerio, and Oryzias dancena. Recent studies have demonstrated that several teleost FXYD isoforms are expressed in the gills and kidneys of the fish, and their expression levels are altered in response to salinity changes, suggesting that these FXYDs may regulate electrolyte homeostasis and body fluid of the fish.

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gi 530537257  1 MSQLTELVLLTVFLALFSRAEANPFVYNYEALRIGGLVFTCVLVAGAVTALCWGQCKPKRK 61
Cdd:cd20329   1 MGHLTLVAVLAVLFSLFMETEANPFVYNYERLRIGGLVFACLLVAGGISVLLYNKCSRKNK 61

FXYD domain-containing ion transport regulator 11; FXYD domain-containing ion transport regulator 11 (FXYD11) is a putative regulatory subunit of the Na(+)/K(+)-ATPase (NKA) pump. FXYD11 is expressed predominantly in the gills of euryhaline teleosts, such as the spotted scat, Scatophagus argus. It regulates NKA activity through protein-protein interactions. The regulation of NKA and FXYD11 is of critical importance for osmotic homeostasis. The expression and activity of NKA, as well as FXYD11 mRNA expression in gills have been shown to respond to different environmental salinity by dual-labeling immunohistochemistry and quantitative PCR (RT-qPCR) methods, indicating that there is an interaction between NKA and FXYD.

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                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530537257  1 MSQLTELVLLTVFLALFSRAEANPFVYNYEALRIGGLVFTCVLVAGAVTALCWGQCKPKRK 61
Cdd:cd20329   1 MGHLTLVAVLAVLFSLFMETEANPFVYNYERLRIGGLVFACLLVAGGISVLLYNKCSRKNK 61

FXYD domain-containing ion transport regulator 11; FXYD domain-containing ion transport regulator 11 (FXYD11) is a putative regulatory subunit of the Na(+)/K(+)-ATPase (NKA) pump. FXYD11 is expressed predominantly in the gills of euryhaline teleosts, such as the spotted scat, Scatophagus argus. It regulates NKA activity through protein-protein interactions. The regulation of NKA and FXYD11 is of critical importance for osmotic homeostasis. The expression and activity of NKA, as well as FXYD11 mRNA expression in gills have been shown to respond to different environmental salinity by dual-labeling immunohistochemistry and quantitative PCR (RT-qPCR) methods, indicating that there is an interaction between NKA and FXYD.

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                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530537257  1 MSQLTELVLLTVFLALFSRAEANPFVYNYEALRIGGLVFTCVLVAGAVTALCWGQCKPKRK 61
Cdd:cd20329   1 MGHLTLVAVLAVLFSLFMETEANPFVYNYERLRIGGLVFACLLVAGGISVLLYNKCSRKNK 61

ATP1G1/PLM/MAT8 family;

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gi 530537257  21 EANPFVYNYEALRIGGLVFTCVL-VAGAVTALCwGQCKPKRK 61
Cdd:pfam02038  2 EDDPFYYDYETLRIGGLIFAGLLfIVGILIILS-KKCKCKFN 42

FXYD domain-containing ion transport regulator 1; FXYD domain-containing ion transport regulator 1 (FXYD1), also known as phospholemman (PLM), or sodium/potassium-transporting ATPase subunit FXYD1, associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which transports Na+ out of the cell and K+ into the cell. It is a plasma membrane substrate for several kinases, including protein kinase A, protein kinase C, NIMA kinase, and myotonic dystrophy kinase. It is thought to form an ion channel or regulate ion channel activity. Transcript variants with different 5' UTR sequences have been described in the literature.

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gi 530537257 21 EANPFVYNYEALRIGGLVFTCVL 43
Cdd:cd20317   3 EHDPFTYDYQSLRIGGLIIAGIL 25

FXYD domain-containing ion transport regulator 3 and similar proteins; This subfamily includes FXYD domain-containing ion transport regulator 3 (FXYD3), FXYD9, and FXYD10, also called PLMS/Phospholemman-like protein. FXYD3, also known as mammary tumor 8 kDa protein (MAT-8), or chloride conductance inducer protein Mat-8, or phospholemman-like (PLML), may function as a chloride channel or as a chloride channel regulator. It associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which transports Na+ out of the cell and K+ into the cell. Two transcript variants encode two different isoforms of the protein; in addition, transcripts utilizing alternative polyA signals have been described in the literature. Members here include mammalians and reptiles. FXYD9 is present in teleosts including: Danio rerio, Atlantic salmon, and Japanese Medaka fish. In general, the FXYD9 isoform has the highest degree of conservation among the examined teleost species, indicating that it may be involved in physiological processes that are not evolving within this group of vertebrates. FXYD10, present in shark, associates with and modifies the activity of Na,K-ATPase in vitro through interactions mediated by its transmembrane and cytoplasmic C-terminal domains. It is important in the phosphorylation and potassium deocclusion reactions, which are known to be controlled by A domain movements. It is thought that FXYD10 interacts with the A domain of the shark Na,K-ATPase alpha-subunit.

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gi 530537257 21 EANPFVYNYEALRIGGLVFTCVLVAGAVTALCWGQCKPKRK 61
Cdd:cd20328   7 KDSPFYYDWHRLRVGGLICAAVLCAIGIIVLLSGKCKCKFN 47

FXYD domain-containing ion transport regulator 4; FXYD domain-containing ion transport regulator 4 (FXYD4), also known as CHIF (channel-inducing factor or corticosteroid hormone-induced factor), evokes K+ conductance in oocytes and is localized in the distal parts of the nephron and in the colon. CHIF, a putative K channel regulator, is regulated by aldosterone in the colon and by K+ intake in the kidney.

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gi 530537257 23 NPFVYNYEALRIGGLVFTCVL-VAGAVTALCwGQCKPKRK 61
Cdd:cd20322   8 SPFYYDWESLQLGGMICAGLLcIAGIAFALS-GKCKCKHS 46